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T Le Chevalier

Publications and source records attributed to T Le Chevalier.

204 records · Page 12Linked to original sources

Triangular test and randomized trials: practical problems in a small cell lung cancer trial.

The triangular test has been used to monitor survival data from a randomized trial in patients with small cell lung cancer. The results of consecutive interim analyses and the problems met by the data monitoring committee and the co-ordinators are described. The methods as well as the consequences of the early stopping on the analysis and the results of this trial are discussed. From this experience, we believe that statistical stopping rules--only one of the factors to be taken into account when deciding to stop a trial--should be used with caution. Independent data monitoring committees may be useful in helping to review the ongoing results and advise the participants in the trial.

Antineoplastic Combined Chemotherapy Protocols↗

First-line vinorelbine-mitoxantrone combination in metastatic breast cancer patients relapsing after an adjuvant anthracycline regimen: results of a phase II study.

PURPOSE: Previous studies demonstrated that doxorubicin and vinorelbine combinations in first-line chemotherapy are highly active in metastatic breast cancer. Mitoxantrone is an anthracenedione with low cardiotoxicity, and seems to be effective when combined with vinorelbine after prior exposure to anthracyclines. PATIENTS AND METHODS: Seventy-two patients with metastatic breast cancer were included in a phase II study. All patients had previously received one anthracycline-containing regimen (doxorubicin or epirubicin) in an adjuvant setting. Vinorelbine was administered at 25 mg/m2 in a 20-min intravenous (i. v.) infusion, days 1 and 8. Mitoxantrone was given at 10 mg/m2 (66 patients) or 12 mg/m2 (6 patients) in a slow i.v. infusion on day 1. Courses were repeated every 3 weeks. RESULTS: Sixty-five patients were evaluable for response; the objective response rate was 49% (95% CI: 37-63%), including four complete and 28 partial responses, with a median duration of response of 7 months (range 2.3-27). Median overall survival was 19 months (range 2-48). Grade 3-4 granulocytopenia was observed in 46% of patients. There were 12 admissions (3% of cycles), involving 17% of patients for febrile neutropenia. Seven patients (10%) experienced grade 3 or 4 cardiotoxicity, and 1 patient died of cardiac heart failure. Other side effects were rare and mild. CONCLUSIONS: The vinorelbine and mitoxantrone combination is an active regimen with low toxic complications when cumulative doses of mitoxantrone are limited to 70 mg/m2. The results in this phase II study make it worthwhile including this regimen in a phase III study for patients who have previously received an anthracycline-containing regimen.

Adult↗

Establishment and characterization of five human small cell lung cancer cell lines from early tumor xenografts.

Five small-cell lung carcinoma (SCLC) cell lines were established from xenografted tumor lines. These tumor lines were established after transplantation into nude mice of primary tumors or metastatic foci obtained surgically, from untreated (IRSC-2M, IRSC6M, IRSC-10M and IRSC-61M) or treated patients (IRSC-74M). They were then set-up in culture as parallel cell lines. Histologically, these tumor lines were classified as being of the classic (IRSC-2M, IRSC-10M and IRSC-61M) or intermediate type (IRSC-6M and IRSC74M). Four of these 5 SCLC cell lines grew as floating cell aggregates, while one (IRSC6M) grew as an adherent cell monolayer. Growth rates were slow (doubling times ranged between 120 and 194 h) but could be accelerated (67 to 144 h) by cultivating cells in medium mixed (v/v) with self-conditioned medium. Electron microscopical examination revealed that all SCLC cell lines contained dense core granules, characteristic of their neuroendocrine origin. These cell lines formed colonies in agarose with colony forming efficiencies ranging from 0.02-0.36%. The classic-type cell lines retained their tumorigenic capacity when re-injected intracranially into naive nude mice, whereas the intermediatetype cells did not. Cytogenetic analysis confirmed the human origin of SCLC xenografts and cultured cell lines. Various numerical and structural chromosome abnormalities were found, with deletion in the short arm of chromosome 3 being the most common (4 of the 5 cell lines). Deletions in or loss of the chromosome 10 were also observed. Oncogene expression was studied in 3 representative cell lines (IRSC-10M, IRSC-2M and IRSC-74M). L-myc was overexpressed only in IRSC-74M, while the GRP gene was overexpressed in the classic (IRSC-2M and IRSC-10M) but not in the intermediate-type cells (IRSC-74M). The Ki-ras oncogene was overexpressed in the 3 cell lines, while c-myc, N-myc, Ha-ras, N-ras, erb B2 and sis were not detected in any of them. The 3 cell lines weakly expressed the MDR1 gene, while the GST-pi gene was not expressed. These cell lines constitute a multifaceted well-characterized in vitro model for studying the biology of these phenotypically diverse cancer cells.

Animals↗